PD

Question 1

A53T mutation in SNCA

Answer 1

Polymeropoulos et al., 1996

Question 2

E46K mutation in SNCA

Answer 2

Zarranz et al., 2004

Question 3

A30P mutation in SNCA

Answer 3

Kruger et al., 1998

Question 4

a-syn -/- mice exhibit reduced striatal DA and attenuated DA-dependent locomotor response to amphetamine

Answer 4

Abeliovich et al., 2000

Question 5

A53T and A30P cause OLIGOMERISATION not fibrillation – cytotoxic oligomers?

Answer 5

Conway et al., 2000

Question 6

Motor impairment and loss of DA terminals was seen in a-syn transgenic mice, in the presence of non-fibrillar a-syn inclusions

Answer 6

Masliah et al., 2000

Question 7

However, transgenic mice over-expressing the protofibrillogenic A30P mutant a-syn failed to exhibit neurodegeneration

Answer 7

Lee et al., 2002

Question 8

Parkin found in 50% early onset cases

Answer 8

Lucking et al., 2000

Question 9

UCHL1 - a couple of variant genes have been found. But some are asymptomatic so involvement is contentious

Answer 9

Moore et al., 2005

Question 10

In cultured cells, overexpression of DJ1 protects against oxidative stress, whereas knockdown enhances susceptibility

Answer 10

Tiara et al., 2004

Question 11

LRRK2 encodes…

Answer 11

Dardarin

Question 12

LRRK2 has been found in various cases

Answer 12

Moore et al., 2005

Question 13

Increased markers of oxidative stress in PD e.g. BAX

Answer 13

Tatton et al., 2003

Question 14

6-OH-DA Adv

Answer 14

Selective DA neuron loss. Adv quantifiable circling behaviour. Tieu, 2011

Question 15

6-OH-DA disadv

Answer 15

lacks progressive pathology

Question 16

IN 1980s drug users displayed severe PD sx. Found to be MPTP contaminant MPP

Answer 16

Langston, 1983

Question 17

MPTP MoA

Answer 17

MPTP lipophilic, crosses BBB and is metabolised into toxic MPP+ by MAO-B –> released from astrocytes and aken up by DA neurons by DAT –>
MPP+ inhibits mitochondrial complex I –> less ATP, oxidative stress. Is sequestered into vesicles by VMAT

Question 18

MPTP adv

Answer 18

preferential damage to nigrostriatal pathway

Question 19

MPTP disadv

Answer 19

no classical LBs

Question 20

Study found that chronic infusion of MPTP caused inclusions immunoreactive to a-syn + ubiquitin

Answer 20

Fornai, 2005

Question 21

Paraquat adv

Answer 21

a-syn inclusions

Question 22

Paraquat disadv

Answer 22

not known if selective for DA toxicity

Question 23

Paraquat MoA

Answer 23

unknown mechanism involving NADPH oxidase and NO synthase –> superoxides (toxic)

Question 24

Rotenone + paraquat use linked to PD in farmers

Answer 24

Tanner et al., 2011

Question 25

inhibits mito complex 1

Answer 25

MPP, rotenone

Question 26

DA neurons in a-syn knockout mice are resistant to MPTP-induced toxicity

Answer 26

Klivenyi et al., 2006

Question 27

and mice overexpressing a-syn are more susceptible to paraquat toxicity

Answer 27

Norris et al., 2007

Question 28

Quaking mouse mutant: spontaneous deletion of parkin. Mice show myelin deficiency and enhanced DA metabolism. Mice display behavioural deficits + tremor

Answer 28

Nikulina et al., 1995

Question 29

Knockout mice have progressive motor abnormalities and deficits in sensorimotor integration. Paradoxically mice have increased basal release of striatal DA, and reduced striatal neuronal excitability

Answer 29

Parkin

Question 30

Dopa to dopamine by

Answer 30

DOPA decarboxylase

Question 31

Blocks dopa decarboxylase

Answer 31

Carbidopa

Question 32

Tyrosine to dopa

Answer 32

Tyrosine hydroxylase

Question 33

MAO-B breaks DA into….

Answer 33

DOPAC

Question 34

MAO-B breaks 3-MT into…

Answer 34

HVA

Question 35

COMT breaks DA into….

Answer 35

3-MT

Question 36

COMT breaks DOPAC into….

Answer 36

HVA

Question 37

Breaks DA into 3MT

Answer 37

COMT

Question 38

Breaks 3MT into HVA

Answer 38

MAO-B

Question 39

Breaks DA into DOPAC

Answer 39

MAO-B

Question 40

Breaks DOPAC into HVA

Answer 40

COMT